A Noninvasive Score Model for Prediction of NASH in Patients with Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease.
Aims. To develop a noninvasive score model to predict NASH in patients with combined CHB and NAFLD. Objective and Methods. 65 CHB patients with NAFLD were divided into NASH group (34 patients) and non-NASH group (31 patients) according to the NAS score. Biochemical indexes, liver stiffness, and Controlled Attenuation Parameter (CAP) were determined. Data in the two groups were compared and subjected to multivariate analysis, to establish a score model for the prediction of NASH. Results. In the NASH group, ALT, TG, fasting blood glucose (FBG), M30 CK-18, CAP, and HBeAg positive ratio were significantly higher than in the non-NASH group (P < 0.05). Multivariate analysis showed that CK-18 M30, CAP, FBG, and HBVDNA level were independent predictors of NASH. Therefore, a new model combining CK18 M30, CAP, FBG, and HBVDNA level was established using logistic regression. The AUROC curve predicting NASH was 0.961 (95% CI: 0.920-1.00, cutoff value is 0.218), with a sensitivity of 100% and specificity of 80.6%. Conclusion. A noninvasive score model might be considered for the prediction of NASH in patients with CHB combined with NAFLD.


Phamtom limb; some theories.
After discussing the problems of elderly amputees with a peripheral vaxcular surgeon, some of the relevant literaure is surveyed, with views from different specialists, none of whom claim understanding nor consistent success in treatment of phantom limb complaints at present. Dorsal column stimulation has still to be evaluated. Psychological aspects indicate a need for a multidisciplinary team approach to this problem.


Prospective relevance of fruit and vegetable consumption and salt intake during adolescence for blood pressure in young adulthood.
Fruit and vegetable (FV) consumption and salt intake are known dietary influences on blood pressure (BP) in adults, but data on their long-term relevance during growth for later BP are rare. We aimed to examine the independent and concomitant influences of adolescent FV and salt intakes on BP in young adulthood. In total, 206 participants (108 males) provided a plausible BP measurement in young adulthood (18-25 years) as well as three repeated 3-day weighed dietary records, 24-h urine samples and BP measurements during adolescence (11-16 years). FV intake was assessed based on dietary records and its urinary biomarkers such as potassium, oxalate and hippuric acid. Urinary sodium chloride (NaCl) was used to estimate salt intake. Prospective associations of adolescent FV and salt intake with adult BP were examined in sex-stratified linear regression models. In multivariable models, a 100 g higher FV intake during adolescence was prospectively related to 0.9 mmHg lower systolic BP in young adult females (P = 0.02), but not in males (P = 0.8). Biomarkers supported the findings for FV regarding systolic BP. Concurrently, a 1 g higher salt intake was related to 1.7 mmHg higher systolic BP in young men only (P = 0.01). For diastolic BP, results were inconsistent. Our findings suggest that in adolescent healthy girls, a higher FV intake may be more relevant for BP than a reduced salt intake and the opposite appears to apply for boys. The physiological implications of the observed sex-specific diet-BP relationships need deeper examination.


Quality of life survey among day release patients at View Road Hospital.
The aim of this study was to identify factors that contributed to the chronic patient's quality of life from both the patients' and staff's point of view. We were also interested in any lack of congruence between staff and patient perception as these could have significant implications for planning long-term care. Fifty of the patients under the Day Release Scheme at View Road Hospital and their staff were given a modified questionnaire concerning the patients' quality of life. Generally the patients reported satisfaction with life domain items covering their living conditions. The majority felt safe in the current setting, enjoyed their work, their regular outings and parole to the nearby shopping centers. Significant differences were observed between the staff and patients' perception in life domain items relating to general well-being, knowledge and education, relationships, in-patient care, leisure and vocational rehabilitation. The staff group perceived having good food, money, good treatment and in employment as being important to their patients' well-being. Patients emphasised having money, family support or a partner, being employed, having time for recreational activities and eating good food. Having good health, medication and feeling at peace were also considered important by many of our patient. The findings of the study are discussed with regard to implications in planning rehabilitation services and improving the quality of care given to patients.


Renomedullary antihypertensive function in accelerated (malignant) hypertension. Observations on renomedullary interstitial cells.
The antihypertensive function of the renal medulla was tested on accelerated (malignant) hypertension of the rabbit. A procedure for the development of accelerated hypertension of the rabbit of lethal proportions within 3 wk was established. This procedure consisted of the application of a rigid clip with a fixed and unyielding gap to the left renal artery and removal of the right kidney. Three additional manipulations, other than simple nephrectomy, were performed on the right kidney after application of the rigid clip to the left renal artery. These were: (a) a sham operation, (b) removal of the kidney and separation of the renal cortex and its autotransplantation in a fragmented state, and (c) removal of the kidney and separation of the renal medulla and its autotransplantation in a fragmented state. After the sham-operated kidney and autotransplanted renal medulla, the standardized accelerated hypertension did not develop, whereas after autotransplanted renal cortex it did. After a period of protection against accelerated hypertension, removal of either the sham-operated kidney or the renomedullary transplants was followed by a prompt rise in arterial pressure and death of the animal. Thus, the antihypertensive action of renomedullary tissue was similar to that of the whole kidney. The main cell type noted in the protective renomedullary transplants had the microscopic characteristics of the lipid-containing interstitial cells. These cells occurred in clusters, often were near capillaries, and appeared hyperplastic. It is suggested that the renomedullary interstitial cell is the most eligible cell for exertion of the renomedullary antihypertensive action. Since vasoactive lipids are extractable from the renal medulla and its interstitial cells, the hypothesis that interstitial cells secrete antihypertensive substance(s) is attractive.


Oral lesion as unusual first manifestation of multiple myeloma: case reports and review of the literature.
Extramedullary plasmacytoma (EMP) and solitary bone plasmacytoma (SBP) represent a disease continuum through a multistage process of cell differentiation, survival, proliferation, and dissemination, strictly related to multiple myeloma (MM), the second most common hematological malignancy. Herein, we report two cases of recurrent oral plasmacytoma progressed to MM, in which the first clinical sign of a more widespread disease was limited to the mouth. Based on our experience, we recommend a strict workup for the differential diagnosis between EMP, SBP, and MM for patients with oral plasmacytoma, including radiological exam of the skeleton, magnetic resonance imaging (MRI) of the bone, and positive emission tomography (FDG-PET). MRI and possibly PET can all be used to more sensitively detect EM plasmacytoma sites.


Methionine uptake via the SLC43A2 transporter is essential for regulatory T-cell survival.
Cell death, survival, or growth decisions in T-cell subsets depend on interplay between cytokine-dependent and metabolic processes. The metabolic requirements of T-regulatory cells (Tregs) for their survival and how these are satisfied remain unclear. Herein, we identified a necessary requirement of methionine uptake and usage for Tregs survival upon IL-2 deprivation. Activated Tregs have high methionine uptake and usage to S-adenosyl methionine, and this uptake is essential for Tregs survival in conditions of IL-2 deprivation. We identify a solute carrier protein SLC43A2 transporter, regulated in a Notch1-dependent manner that is necessary for this methionine uptake and Tregs viability. Collectively, we uncover a specifically regulated mechanism of methionine import in Tregs that is required for cells to adapt to cytokine withdrawal. We highlight the need for methionine availability and metabolism in contextually regulating cell death in this immunosuppressive population of T cells.


Determinants of the maximal change in pleural pressure during tidal breathing in COPD-affected horses.
In six COPD-affected horses, we analysed the factors responsible for the changes in pleural pressure (delta Pplmax) that occur during tidal breathing. Four-hundred-and-sixty-eight measurements of each parameter: pulmonary resistance (RL), dynamic elastance (Edyn), air flow rates, and the timing of breathing, were gathered during a trial of the bronchodilator pirbuterol. Data were placed into seven ranks, based on the magnitude of delta Pplmax; rank 1: 5-15; rank 2: 15-25; rank 3: 25-35; rank 4: 35-45; rank 5: 45-55; rank 6: 55-65; and rank 7 > 65 cm H2O. Up to rank 4 (45 cm H2O), the increase in delta Pplmax was due to increases in RL, Edyn, and inspiratory and expiratory air flow rates. Further increases in delta Pplmax were due to continuing increases in Edyn and flow rates with little change in resistance. The increase in inspiratory flow rates was the result of a decrease in inspiratory time. The large increase in peak expiratory flow could not be explained by the small decrease in expiratory time and must therefore be due to a change in breathing strategy as delta Pplmax increased. Changes in air flow rates as well as changes in RL and Edyn must be considered as reasons for a change in delta Pplmax when evaluating horses with COPD.


Changes in Cortical Activation Patterns in Language Areas following an Aerobic Exercise Intervention in Older Adults.
Previous work has shown that older adults who evidence increased right inferior frontal gyrus (IFG) activity during language tasks show decreased sematic verbal fluency performance. The current study sought to evaluate if an aerobic exercise intervention can alter patterns of brain activity during a semantic verbal fluency task assessed by functional magnetic resonance imaging (fMRI). Thirty-two community-dwelling, sedentary older adults were enrolled to a 12-week aerobic "Spin" exercise group or a 12-week nonaerobic exercise control condition (Balance). Thirty participants completed their assigned intervention (16 Spin; 14 Balance) with pre- and postintervention assessments of a semantic verbal fluency task during fMRI and estimated VO2max testing. There was a significant increase in the change scores for estimated VO2max of the Spin group when compared to the Balance group. Semantic verbal fluency output within the scanner was also improved in the Spin group as compared to controls at postassessment. Group fMRI comparisons of IFG activity showed lower activity in the right IFG following the intervention in the aerobic Spin group when compared to the Balance group. Regression analysis of imaging data with change in both estimated VO2max and semantic verbal fluency was negatively correlated with activity in right IFG. The current work is registered as clinical trial with NCT01787292 and NCT02787655.


Stress-induced mutagenesis in bacteria.
Bacteria spend their lives buffeted by changing environmental conditions. To adapt to and survive these stresses, bacteria have global response systems that result in sweeping changes in gene expression and cellular metabolism. These responses are controlled by master regulators, which include: alternative sigma factors, such as RpoS and RpoH; small molecule effectors, such as ppGpp; gene repressors such as LexA; and, inorganic molecules, such as polyphosphate. The response pathways extensively overlap and are induced to various extents by the same environmental stresses. These stresses include nutritional deprivation, DNA damage, temperature shift, and exposure to antibiotics. All of these global stress responses include functions that can increase genetic variability. In particular, up-regulation and activation of error-prone DNA polymerases, down-regulation of error-correcting enzymes, and movement of mobile genetic elements are common features of several stress responses. The result is that under a variety of stressful conditions, bacteria are induced for genetic change. This transient mutator state may be important for adaptive evolution.


Protein-losing enteropathy in an infant with rotavirus infection.
Protein-losing enteropathy (PLE) is a rare gastro-intestinal complication characterised by intestinal loss of proteins with consequent hypoproteinaemia and generalised oedema. Rotavirus infection associated with PLE in children has rarely been reported. A 6-month-old girl presented with diarrhoea, fever and generalised oedema. Total serum proteins were 34 g/L (61-79) and plasma albumin 16.8 g/L (40-50), serum sodium was 126 mmol/L and there was mild metabolic alkalosis (pH 7.46). Stool for alpha-1 antitrypsin was >1.2 mg/g (<0.6) which supported the diagnosis of PLE. Stool examination demonstrated the presence of rotavirus antigen by the rapid immunochromatographic test. Abdominal ultrasound showed bowel distension and intestinal wall thickening with a small amount of ascites. Echocardiography excluded pericardial effusion. Two albumin infusions (1 g/kg) were required to sustain normal serum albumin levels. Over the next 2 weeks, there was gradual normalisation of stools and progressive reduction of oedema. In children with acute and symptomatic PLE, rotavirus should be considered in the differential diagnosis. The availability of the rapid immunochromatographic test facilitates the diagnosis. In most cases, supportive care alone is sufficient, but albumin infusions may be required in more severely affected children.


Hypertrophic non-union of the first rib causing thoracic outlet syndrome: a case report.
We experienced a rare case of thoracic outlet syndrome caused by hypertrophic nonunion of the first rib. A diagnosis was made mainly upon provocative tests and imaging studies. Pain and tingling could be reproduced and the radial pulse obliterated by the hyperabduction test. Abundant callus formation on the posterior aspect of the first rib with fracture line was visible on plain radiograph. Two-dimensional computed tomography showed right thoracic outlet narrowing mainly caused by the mass-effect of the callus. Dynamic arteriographic studies revealed an external compression of the right subclavian artery and duplex ultrasonography demonstrated a reduction in right subclavian artery blood flow when the shoulder is in 90 degrees of abduction. Surgery was performed after the conservative management for three months which failed to relieve the patient of his complaints. Resection of the first rib via transaxillary approach was undergone uneventfully in combination with the myotomy of the scalenus anticus muscle. At postoperative one year follow up, the patient was free of symptoms, and had a full range of motion of the right shoulder with no evidence of arterial insufficiency.


An Inhibitor of Activated Blood Coagulation Factor X Shows Anti-Endothelial Senescence and Anti-Atherosclerotic Effects.
Coagulant factor Xa inhibitors (XaIs) are prescribed for patients with atrial fibrillation for years. Human umbilical venous endothelial cells (HUVECs) were cultured with or without (w/wo) a XaI (rivaroxaban) under high glucose (HG: 22 mM). Endothelial senescence was investigated by assessing senescence-associated-β-galactosidase (SA-β-gal), p53, and telomere length. Endothelial function and atherosclerosis were examined by nitric oxide-related-products (NOx: NO2- and NO3-), O2-, endothelial NO synthase (eNOS), NADPH oxidase (p22phox), and ICAM1. PAR1 (protease-activated receptor 1) and PAR2, which were reported to regulate eNOS phosphorylation, were inhibited by small interfering RNAs (siRNAs). Thirty-two male dyslipidemic type 2 diabetic rats (ZFDM LepRfa/fa) were fed a high-cholesterol diet w/wo XaI (50 µg/day/kg) for 1-4 weeks. SA-β-gal, p53, p21, and p16INK4a were increased by HG and restored by XaI (50 nM) in HUVECs. XaI restored telomerase activity and preserved telomere length. XaI suppressed O2-, p22phox, and ICAM1 and restored NOx and eNOS. XaI decreased PAR1 following elevation by HG, which was confirmed by PAR1 siRNA and PAR2 siRNA. In in vivo experiments, plasma glucose, total cholesterol, and triglycerides were increased for 4 weeks but were not changed by XaI. XaI decreased SA-β-gal and telomerase and preserved telomere length in the aortic endothelium. XaI activated eNOS, inhibited p22phox, increased plasma NOx, and decreased O2-. Rivaroxaban prevents replicative senescence in HUVECs and aortic endothelial cells in dyslipidemic diabetic mice. It restores endothelial function and prevents the progression of atherosclerosis.


Clinical Outcomes and Techniques for Radiofrequency Ablation of Lung Tumors Smaller than 1 cm.
To evaluate the outcomes of radiofrequency ablation (RFA) on lung tumors < 1 cm in maximum diameter. Twenty-eight patients (12 male, 16 female; median age, 59 years; mean age, 58 ± 16 years; range, 16-78 years) who underwent RFA for lung tumors < 1 cm in diameter between November 2009 and September 2018 were included in this study. Thirty-five tumors (median size, 8.4 mm; mean size, 7.7 ± 1.9 mm; range, 3.6-9.9 mm) were treated with 33 sessions of RFA. Technique efficacy and safety were subsequently evaluated. Initial and secondary technique efficacy were defined as complete ablation without residual tumor or local tumor progression after initial and repeat RFA, respectively. Safety was evaluated according to the Common Terminology Criteria for Adverse Events, version 5.0. Residual tumor remained for 1 tumor (3%, 1/35) and local tumor progression was found in 2 tumors (6%, 2/35). Initial technique efficacy rate was therefore 91% (32/35). The remaining 3 tumors were treated by repeat RFA (secondary technique efficacy rate: 100%, 35/35). Initial technique efficacy rate was significantly lower for tumors treated with starting energy ≥ 20 W (P = 0.02) and showing a quick increase in tissue impedance (P = 0.01). There were 4 grade 2 adverse events (12%, 4/33) comprising pneumothorax requiring chest tube placement, and 14 grade 1 adverse events comprising self-limiting pneumothorax (36%, 12/33) and pulmonary parenchymal hemorrhage (6%, 2/33). To achieve good outcomes for lung tumors < 1 cm, radiofrequency energy should be started at < 20 W. Application of manual mode ablation might be considered when delivery of power cannot be continued due to a quick increase in tissue impedance.


When technical achievements aren't enough: Lessons learned from efforts to catalyze policy action on supply chain in Senegal.
Before 2013, Senegal public health supply system was pull-based and fully public-run. Lengthy and recurrent stockouts of essential health products (incl. contraceptives) were the rule, not the exception as they used to strike more than 80% of public service delivery points (SDPs). Following a successful pilot in two districts in 2012, the Senegalese Ministry of Health and Social Action (MSAS) implemented the Informed Push Model (IPM) Project (2013-2016). In its first two years, IPM bridged key gaps and expanded the distribution of contraceptives by private third party logistics operators to all public SDPs in Senegal and nearly eliminated stockouts. However, the MSAS was slow to take ownership of the project. Understanding the roots of this reluctance, executing a range of targeted communication and advocacy efforts and preparing a strong transition plan are succeeding to push Government toward full ownership to enable the National Supply Pharmacy to distribute all health products going to SDPs, including vaccines, consistently with their Strategic Plan 2014-2018.


Increased expression of heat shock protein 70 in adherent ovarian cancer and mesothelioma following treatment with manumycin, a farnesyl transferase inhibitor.
Since farnesylation by farnesyltransferase (FTase) is the first obligatory step in the signaling transduction pathway of ras p21, FTase has been the target of new anticancer treatment modalities. Famesyl transferase inhibitors (FTIs), a novel class of antitumor drugs that blocks the oncogenic activity of ras, were first developed as therapy for ras-mutated human tumors. FTIs are also capable of inhibiting tumors without ras mutations, while different mechanisms of cell growth inhibition by FTI have been proposed. In cell culture and in animal models, FTIs have been shown to be potent inhibitors of cancer cell growth. We showed that manumycin, a farnesyl pyrophosphate competitive inhibitor, inhibits ovarian and mesothelioma cancer cell growth. To examine the molecular changes after exposure to manumycin, total proteins from treated and untreated 2774 cell line were extracted and separated by two dimensional gel electrophoresis (2-DE) and detected by colloidal coomassie blue staining. The 2-DE was found reliable for comparison of protein profiles before and after manumycin treatment. Two protein spots (spot 1 and 2) appeared after manumycin treatment. Generated peptide peaks were matched by database query (prowl.rockefeller.edu/cgi-bin/ProFound) to a heat shock protein (HSP) and a modified HSP, both with MW 70 KD. The expression status of HSP 70 was confirmed by Western blot and HSP 70 ELISA using an antibody against HSP 70. The expression of HSP70 increased with the length of exposure to, and the dose of manumycin as demonstrated by ELISA. Increase in HSP70 expression was also observed by Western blot after a 48-hour treatment with manumycin in ovarian cancer cell line OVCAR3 and three other cell cultures derived from samples of patients diagnosed with ovarian cancer and mesothelioma. Our study is the first report demonstrating an up-regulation of HSP 70 in ovarian cancer cell lines and mesothelioma cell cultures after treatment with the FTI, manumycin. This up-regulation of HSP 70 may be a cellular mechanism of cell self-protection against the apoptotic process and cell death, and it may enhance resistance and account for the altered sensitivity of certain cancers to FTIs agents. HSPs may therefore be an important molecular target for drug intervention strategies.


Purification, crystallization and preliminary X-ray crystallographic analysis of 3-ketosteroid Δ1-dehydrogenase from Rhodococcus erythropolis SQ1.
3-Ketosteroid Δ(1)-dehydrogenase plays a crucial role in the early steps of steroid degradation by introducing a double bond between the C1 and C2 atoms of the A-ring of its 3-ketosteroid substrates. The 3-ketosteroid Δ(1)-dehydrogenase from Rhodococcus erythropolis SQ1, a 56 kDa flavoprotein, was crystallized using the sitting-drop vapour-diffusion method at room temperature. The crystals grew in various buffers over a wide pH range (from pH 5.5 to 10.5), but the best crystallization condition consisted of 2%(v/v) PEG 400, 0.1 M HEPES pH 7.5, 2.0 M ammonium sulfate. A native crystal diffracted X-rays to 2.0 Å resolution. It belonged to the primitive orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 107.4, b = 131.6, c = 363.2 Å, and contained eight molecules in the asymmetric unit. The initial structure of the enzyme was solved using multi-wavelength anomalous dispersion (MAD) data collected from a Pt-derivatized crystal.


A distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer.
Lipids are known to influence tumour growth, inflammation and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The levels of 46 lipids were individually prognostic and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0) and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome.


Effects of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.
Male and female Wistar strain rats were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water for 6 weeks and then water without BBN for 18 weeks. Diethylstilbestrol and testosterone were implanted subcutaneously into both intact and gonadectomised animals before or after treatment with BBN to evaluate their effects on the development of bladder tumours. Diethylstilboestrol reduced the incidence of bladder tumours significantly in male rats. The incidence was higher in female rats after spaying and administration of testosterone after BBN treatment, than in the intact female. These results suggest that diethylstilboestrol inhibits carcinogenesis of the urinary bladder induced by BBN and growth of bladder tumours induced by BBN, in male rats. On the other hand, testosterone seems to stimulate the growth of bladder tumours induced by BBN in female rats.


Biochemical indicators related to antioxidant status and bone metabolic activity in Finnish elderly men.
Serum concentrations of vitamins A, D and E, osteocalcin, calcium, selenium, cholesterol and HDL-cholesterol were measured in 270 elderly Finnish men aged from 65 to 84 years. alpha-Tocopherol and selenium decreased with aging as did 25-hydroxyvitamin D. Low serum levels were found especially for 25-hydroxyvitamin D (19% less than 8 micrograms/l), selenium (45% less than 70 micrograms/l) and osteocalcin (52% less than 1.8 micrograms/l). Men living in institutions for the aged had lower serum 25-hydroxyvitamin D levels than those living at home. Smoking was associated with decreased and alcohol consumption with increased serum levels of 25-hydroxyvitamin D. Those men who reported having most weekly working hours had highest serum levels of 25-hydroxyvitamin D. Serum osteocalcin correlated with 25-hydroxyvitamin D at normal or high serum vitamin levels but not at low vitamin levels; neither did it correlate with age or consumption of tobacco, alcohol or multivitamin pills.


Randomized Comparison of 3 High-Level Disinfection and Sterilization Procedures for Duodenoscopes.
Duodenoscopes have been implicated in the transmission of multidrug-resistant organisms (MDRO). We compared the frequency of duodenoscope contamination with MDRO or any other bacteria after disinfection or sterilization by 3 different methods. We performed a single-center prospective randomized study in which duodenoscopes were randomly reprocessed by standard high-level disinfection (sHLD), double high-level disinfection (dHLD), or standard high-level disinfection followed by ethylene oxide gas sterilization (HLD/ETO). Samples were collected from the elevator mechanism and working channel of each duodenoscope and cultured before use. The primary outcome was the proportion of duodenoscopes with an elevator mechanism or working channel culture showing 1 or more MDRO; secondary outcomes included the frequency of duodenoscope contamination with more than 0 and 10 or more colony-forming units (CFU) of aerobic bacterial growth on either sampling location. After 3 months of enrollment, the study was closed because of the futility; we did not observe sufficient events to evaluate the primary outcome. Among 541 duodenoscope culture events, 516 were included in the final analysis. No duodenoscope culture in any group was positive for MDRO. Bacterial growth of more than 0 CFU was noted in 16.1% duodenoscopes in the sHLD group, 16.0% in the dHLD group, and 22.5% in the HLD/ETO group (P = .21). Bacterial growth or 10 or more CFU was noted in 2.3% of duodenoscopes in the sHLD group, 4.1% in the dHLD group, and 4.2% in the HLD/ETO group (P = .36). MRDOs were cultured from 3.2% of pre-procedure rectal swabs and 2.5% of duodenal aspirates. In a comparison of duodenoscopes reprocessed by sHLD, dHLD, or HLD/ETO, we found no significant differences between groups for MDRO or bacteria contamination. Enhanced disinfection methods (dHLD or HLD/ETO) did not provide additional protection against contamination. However, insufficient events occurred to assess our primary study end-point. ClinicalTrials.gov no: NCT02611648.


[Retroaldol cleavage of the glyopeptide antibiotic ristomycin A during alkaline inactivation].
The chemical and physicochemical characteristics of one of the two inactive components, i.e. the reduced product of alkaline inactivation (PAH-II) of ristomycin. A were studied. The components formed on the antibiotic incubation in mild alkaline media: 0.05 M NaOH, 37 degrees C, 1.5-2 hours. It was shown that the retroaldol cleavage of the C alpha-C beta bond of the phenol serine fragment of the trinuclear dideschlorvancomycinic acid G at the aglycone N-end was one of the causes of ristomycin A rapid inactivation under such conditions.


Degradation and reutilization of alveolar phosphatidylcholine by rat lungs.
We have shown previously that phospholipids instilled through the trachea are removed from the air spaces in isolated rat lungs by a process that is stimulated by beta-adrenergic agonists. In this study, we evaluated the fate of radiolabeled lipid vesicles [50% [3H]dipalmitoyl phosphatidylcholine (DPPC), 25% phosphatidylcholine (PC), 15% cholesterol, and 10% phosphatidylglycerol (PG)]. Vesicles were instilled through the trachea of anesthetized rats, and the lungs removed for perfusion. The percent of instilled 3H that could not be removed from lungs by extensive lung lavage increased progressively; at 3 h this fraction was 25.8 +/- 0.63% (mean +/- SE; n = 8). The percent of dpm in the lung homogenate accounted for by PC decreased progressively while dpm in lyso-PC, unsaturated PC, and aqueous soluble metabolites [choline, choline phosphate, glycerophosphorycholine, and cytidine 5'-diphosphate (CDP) choline (CDP-choline) increased. The dpm in microsomal and lamellar body fractions isolated from lung homogenates also increased progressively with time of perfusion. The presence of 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) significantly stimulated both uptake of DPPC and the appearance of radioactivity in metabolites and subcellular organelles. This effect of 8-BrcAMP was not due to stimulation of phospholipase A activity. These results indicate that exogenous phospholipids instilled into the air spaces of rat lungs are internalized and degraded by a process that is stimulated by cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)


T cells in the human metastatic melanoma microenvironment express site-specific homing receptors and retention integrins.
T-cell infiltration into the metastatic melanoma microenvironment (MME) correlates with improved patient survival. However, diffuse infiltration into tumor occurs in only 8% of melanoma metastases. Little is known about mechanisms governing T-cell infiltration into human melanoma metastases or about how those mechanisms may be altered therapeutically. We hypothesized that T cells in the MME would be enriched for chemokine receptors CCR4, CCR5, CXCR3 and homing receptors relevant to the tissue site. Viably cryopreserved single cell suspensions from nineteen melanoma metastases representing three metastatic sites (tumor-infiltrated lymph node, skin and small bowel) were evaluated by multiparameter flow cytometry and compared to benign lymph nodes and peripheral blood mononuclear cells from patients with Stage IIB-IV melanoma. T cells in the melanoma metastases contained large effector memory populations, high proportions of activated, moderately differentiated cells and few regulatory T cells. Site-specific homing was suggested in bowel, with high expression of CCR9. We neither encounter the anticipated enrichment of integrin α4β7 in bowel, cutaneous leukocyte antigen (CLA) in skin, nor integrin α4β1 or receptor CXCR3 in metastatic sites. Retention integrins αEβ7, α1β1 and α2β1 were significantly elevated in metastases. These data suggest limited tissue site-specific homing to human melanoma metastases, but a significant role for retention integrins in maintaining intratumoral T cells. Our findings also raise the possibility that T-cell homing, infiltration, and retention in melanoma metastases may be increased by increasing expression of ligands for CLA, α4β1 and CXCR3 on intratumoral endothelium.


Prophylactic and curative effects of recombinant human superoxide dismutase in lethal rat endotoxemia.
The continuous infusion of E. coli lipopolysaccharide (100 mg/kg in 4 h) caused a 100%-mortality in pentobarbital-anesthetized rats within 6 h. Recombinant human superoxide dismutase (r-HSOD) infused concomitantly with the E. coli endotoxin dose-dependently (0.1-1.0 mg/kg per min) increased survival rate up to 90%. Significant improvement of survival rate was also obtained when r-HSOD-infusion (0.464 mg/kg per min) was only started up to 3 h after beginning of the endotoxin application. Also, two single bolus injections of r-HSOD (20 mg/kg each) during endotoxemia significantly increased survival rate. Decrease of heart rate was prevented and decline of arterial blood pressure was diminished by r-HSOD (0.464 mg/kg per min) as compared to vehicle-treated endotoxemic rats. Lactic acidosis occurred with no significant statistical difference between r-HSOD- and vehicle-treated groups. Increase of hematocrit in endotoxemic control rats was balanced by fluid uptake. In contrast, in the groups treated with endotoxin plus r-HSOD or saline alone hematocrit decreased identically. Decrease of whole blood leukocytes (to 30.2 +/- 9.5% of baseline in endotoxemic controls) was less pronounced in the r-HSOD group (fall to 49.2 +/- 6.5% of baseline), but this difference did not reach statistical significance. Marked thrombocytopenia (to 12.9 +/- 3.2% of baseline) and consumption of plasma fibrinogen (to 39.5 +/- 10.3% of baseline) were significantly attenuated in r-HSOD-treated rats, where thrombocytes only decreased to 28.1 +/- 3.6% and plasma fibrinogen to 76.6 +/- 5.0% of baseline values at the end of endotoxin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term management of GERD. Why using endoscopy just now?
Early results with the use of endoscopic techniques in the treatment of gastro-oesophageal reflux disease (GERD) have been recently reported. Methods used are an injection of biocompatible substances within the lower oesophageal sphincter (LES), LES ablation using radio-frequency, and suture of folds in the area distal to the Z-line. The latter--endoscopic gastroplasty--is most difficult, but this technique has been most widely accepted by gastroenterologists to this date. Effectiveness of these endoscopic management systems in the long-term control of GERD has never been compared to a control group. This fact, together with the proven efficacy of anti-secretory drugs and the refinement of laparoscopic surgery during the past few years, has led physicians to be more demanding regarding early results. This review will discuss each method available, and issues answered by reported studies to this day are approached.


The effect of pre-exposure to 0.12 ppm of ozone on exercise-induced asthma.
Ozone (O3) is a common air pollutant that has been associated with a dose-dependent increased bronchial responsiveness and airway inflammation. Previous investigations have shown increased airway responsiveness to allergens in asthmatics pre-exposed to 0.12 ppm of O3 for 1 h. In the present study, we investigated whether inhalation of relatively low levels of O3 would modify the degree of exercise-induced bronchoconstriction. We studied 15 "never smokers" with mild stable asthma (7 male and 8 female) (mean age [+/- SD] 25.6 +/- 6.8 years) who had exhibited a fall in FEV1 > 15 percent after a standard 6-min treadmill exercise challenge test on the screening day. This was a double-blind, placebo-controlled study. The patients were randomized to receive either O3 or air (placebo) before performing the exercise challenge again. The average highest 1-h daily O3 concentrations in Toronto during O3 days and air days were 0.017 +/- 0.017 and 0.014 +/- 0.005 ppm, respectively. The O3 concentration inside the chamber averaged 0.122 +/- 0.005 ppm on O3 days and 0.002 +/- 0.001 on placebo days. Partial and complete flow volume curves were done before and after this exposure, and also 5, 10, 15, 20, 30, and 60 min postexercise. The percent fall in FEV1 on the O3 chamber day and on the air chamber day was the same (F = 0.67, p = 0.67, NS) as well as the percent fall in V40p (F = 0.91, p = 0.49, NS). A repeated measures analysis of variance to test the effects of exposure on the time course of the airway response after exercise showed no significant difference between the 2 days. There was also no significant difference in maximal percentage fall in FEV1 (25.6 +/- 8.6) or V40p (62.2+18.6) following O3 exposure, and FEV1 (26.8 +/- 9.4)(p = 0.64) or V40p (65.3+4.31)(p = 0.60) following air. Our data indicate that previous exposure at rest to a concentration of O3 that has previously been shown to augment the bronchoconstriction response to allergens did not increase the bronchoconstriction response to subsequent exercise nor did it change the time course of such bronchoconstriction.


Magnetic resonance imaging for diagnosing, monitoring and prognostication in psoriatic arthritis.
Psoriatic arthritis (PsA) is a chronic systemic, inflammatory disease associated with skin psoriasis. PsA may be difficult to assess with clinical examination and blood tests because of its complex and multifaceted clinical presentation. Magnetic resonance imaging (MRI) can visualise all peripheral and axial joints and entheses involved in PsA, and allow the rheumatologist to assess inflammation and structural damage in detail. In the present paper, we provide a brief overview of MRI to diagnose, monitor and prognosticate in PsA in clinical care.


Survival Function of Clinical and Radiographic Success of Three Obturating Materials in Primary Teeth at 3, 6 and 9 Months Periodic Intervals - A Randomized Controlled Clinical Trial.
The study aims to assess clinically and radiographically the success of zinc oxide eugenol, metapex, and endoflas as root canal obturating materials in primary teeth over 3, 6, and 9 months of time intervals. The randomized controlled trial was performed in 60 primary molars of 36 children aged between 4 and 9 years. Permanent restorations were given and stainless steel crowns were placed for the treated tooth. Comparing the survival proportion between the three groups was done using the Wilcoxon (Gehans) statistical test. The clinical survival variable showed 100% survival proportion for zinc oxide eugenol and endoflas, while for metapex it was 69% at the end of 9 months. The radiographical survival proportion was 100% for zinc oxide eugenol, followed by endoflas at 92% and 58% for metapex group.


Anisotropy and Nanomechanics of Cellulose Nanocrystals/Polyethylene Glycol Composite Films.
The influence of shear flow on the nanomechanical properties of cellulose nanocrystal (CNC)/polyethylene glycol (PEG) composite films and the distribution of anisotropic phases are investigated at various CNC/PEG ratios. Here, the drying process of CNC/PEG mixed suspensions is systematically traced by rheology, followed by the spatial mapping of local mechanical properties of CNC/PEG films by nanoindentation. The detailed study of the morphology of CNC/PEG films by polarized optical microscopy (POM) and image analysis revealed the link between the mechanical properties and the influence of shear flow. A comparison of the data obtained for shear-dried films with nonsheared films showed the improved reduced Young's modulus (Er) and hardness (H), and suppression of microphase separation in the shear-dried films. Based on this experimental evidence, a mechanism is proposed to explain the microstructural transition during the shear-drying process leading to the generation of the anisotropic domains containing the shear-induced assembled structure of CNC particles coexisting with the elongated PEG microphases.


Employer costs of alcohol-involved injuries.
This study estimates the annual cost of alcohol-related injuries to employers in 1998-2000. Incidence was estimated with occupational injury data, motor vehicle crash data and health care data for 1998-2000. Employer costs were estimated from federal estimates of injury costs by source of payment using data on the percentage of varied payment streams (e.g., health insurance, sick leave) paid by employers. The annual employer cost of alcohol-related injuries to employees and their dependents exceed US dollars 28.6 billion. Out of this, US dollars 13.2 billion comes from job-related, alcohol-involved injuries. The annual employer cost of motor vehicle crashes in which at least one driver was alcohol-impaired is over US dollars 9.2 billion. Out of this, only US dollars 3.4 billion comes from job-related alcohol involvement. Safety programs can reduce the fringe benefit bill without reducing the benefits offered to employees.


Myoclonic status epilepticus as a presentation of caspr2 antibody-associated autoimmune encephalitis.
We present a case of autoimmune encephalitis associated with antibodies targeting contact in-associated protein-like 2. This case is notable because of the presentation with myoclonic status epilepticus and the prolonged clinical course of refractory seizures, which are demonstrated in the accompanying videos, and not previously associated with this condition. Treatment with prednisone, intravenous immunoglobulin, plasma exchange, rituximab, cyclophosphamide, and mycophenolate mofetil resulted in significant functional improvement. Historically, myoclonic status epilepticus is associated with a grave prognosis and minimal chance of meaningful recovery. This case demonstrates that autoimmune encephalitis remains an important differential diagnosis in patients with such a presentation, and that early recognition and the appropriate institution of immunotherapy can result in seizure control and functional recovery. [Published with video sequences].


New Horizons in cellular senescence for clinicians.
Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state-the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.


Use of HEAVEN criteria for predicting difficult intubation in the emergency department.
Most airway prediction tools only consider anatomical factors. The HEAVEN criteria incorporate both anatomical and physiological elements, but have never been studied in the emergency department. This study aimed to evaluate the association between HEAVEN criteria and intubation difficulty. We conducted a prospective cross-sectional study from April 1, 2020 to January 31, 2021 in the emergency department of a tertiary public hospital. All patients requiring rapid-sequence or delayed-sequence intubation were included. Patients intubated during cardiopulmonary resuscitation were excluded. We enrolled 174 patients. Study endpoints were first pass success and intubation complications. The presence of any HEAVEN criteria was associated with a decrease in the first pass success rate (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.02-0.43; P < 0.01). The anatomical challenge was the only criterion associated with first pass sucess (OR, 0.13; 95% CI, 0.05- 0.29; P < 0.01), whilst other criteria (hypoxemia, extremes of size, vomit/blood/fluid, exsanguination, and neck mobility) were not (P > 0.05). All anatomical factor criteria were associated with difficult airway view (P < 0.05). Intubation complications occurred more in the presence of hypoxemia (OR, 7.44; 95% CI, 2.82-19.63; P < 0.01) and vomit/blood/fluid (OR, 5.55; 95% CI, 2.39-12.92; P < 0.01). Anatomical challenge in HEAVEN criteria can predict first pass success. All anatomical factors in HEAVEN criteria could predict difficult airway view and peri-intubation hypoxemia could be used to anticipate intubation complications. More validation studies are still needed to evaluate the use of HEAVEN criteria as a predictor tool for difficult airway.


Ichthyobodo salmonis sp. n. (Ichthyobodonidae, Kinetoplastida), an euryhaline ectoparasite infecting Atlantic salmon (Salmo salar L.).
Phylogenetic analyses of SSU rDNA sequences have previously revealed the existence of 2 Ichthyobodo species able to infect Atlantic salmon (Salmo salar L.). Ichthyobodo necator sensu stricto (s.s.) is assumed to be a freshwater parasite, while a genetically distinct but undescribed species, Ichthyobodo sp. II sensu Todal et al. (2004) have been detected on Atlantic salmon in both fresh- and seawater. In the present study a morphological description of Ichthyobodo sp. II from the gills of salmon reared in fresh-, brackish- and seawater is presented, using both light- and electron microscopy. Comparative morphometry show that Ichthyobodo sp. II from both freshwater and seawater displays a different cell shape, and is significantly smaller than I. necator s.s. Also, ultrastructural characteristics distinguish these two species, notably differences in the attachment region and the presence of spine-like surface projections in Ichthyobodo sp. II. Based on both unique SSU rDNA sequences and morphological characteristics, we conclude that Ichthyobodo sp. II. represents a novel species for which we propose the name Ichthyobodo salmonis sp. n.


Calcium antagonists in coronary artery disease.
The introduction of calcium antagonists has had a significant influence on the management of angina pectoris. Whereas, a beta blocker functions by reducing oxygen demand, the calcium antagonists increase oxygen supply and also decrease oxygen demand. The calcium ion is a vital link in excitation-contraction coupling; the regulation of intracellular calcium levels directly modulates cardiac and smooth muscle function. The three agents currently in use are verapamil, nifedipine, and diltiazem; ony the first two are available by prescription at this time. Although all three are calcium channel blocking agents, they differ in their electrophysiologic effects. Verapamil and, to a lesser extent, diltiazem slow AV nodal transmission and are thus helpful in controlling the ventricular rate in atrial fibrillation. All have a negative inotropic property which may limit their use in patients with advanced left ventricular dysfunction.


Radioiodine bronchogram in acute respiratory tract infection.
In this article, the authors described a 31-year-old woman with differentiated thyroid cancer is presented who had radioiodine uptake in the distribution of the tracheobronchial tree in association with symptoms of an acute respiratory tract infection. As expected, the uptake was transient and disappeared on the follow-up scan performed after 10 days of antibiotic treatment


Cancer Vaccines - SMi's Fourth Annual Conference (September 16-17, 2015 - London, UK).
Recent years have seen the academic, medical and pharmaceutical communities gain a new understanding of the central role of the immune system in fighting cancer. With the approval of the first cancer vaccine by the U.S. Food and Drug Administration (FDA) and the success of immuno-oncology, new avenues are opening for the successful development of therapeutic cancer vaccines. Opportunity for combination therapies exploiting immune checkpoint inhibitors is being realized and delivery mechanisms and adjuvants are likewise being optimized. The incorporation of monoclonal antibodies alongside genetically engineered viral vectors is also being pursued. This year's conference focused on the development of personalized therapies and their commercial viability, with in-depth discussions of novel T-cell therapies, oncolytic viruses, gene therapies and adoptive T-cell transfer. The meeting brought together key academic and medical experts with leading industry figures to debate future directions and the next generations of tools in cancer immunotherapy.


A national survey of the management of congenital nasolacrimal duct obstruction in the United kingdom.
To survey national variation in the management of congenital nasolacrimal duct obstruction, particularly the timing of intervention and the use of nasolacrimal intubation, nasal endoscopy, and assistance from an ear, nose, and throat surgeon at different stages of management. A telephone survey was conducted of 100 ophthalmologists in the United Kingdom who were involved in the management of congenital nasolacrimal duct obstruction. A sequential management protocol was established for each, including the nature of procedures, their timing, and the use of nasal endoscopy and ear, nose, and throat surgeons. Of those surveyed, 49% use the dye disappearance test for diagnosis. Eighty-four percent suggest lacrimal sac massage to parents. No surveyed ophthalmologists perform "office" probing or balloon dilation. Seventy-four percent perform initial probing after 1 year, with 25% using nasal endoscopy. If symptoms persist, 64.5% (60 of 93) repeat the probing, whereas 35.5% (33 of 93) intubate the lacrimal system. The use of nasal endoscopy increases to 50.5% (47 of 93). By the third intervention, 77.6% (45 of 58) perform lacrimal intubation, with 72.4% (42 of 58) using nasal endoscopy. All opt for dacryocystorhinostomy as the fourth intervention and 28.3% (13 of 46) perform this procedure themselves, whereas 71.7% (33 of 46) refer the patient to another practitioner. In total, 65% (65 of 100) use tubes at some stage of management, 58% (58 of 100) make some use of nasal endoscopy, and 33% (33 of 100) involve ear, nose, and throat surgeons. Based on the results of this survey, huge variation exists in the management of congenital nasolacrimal duct obstruction in the United Kingdom. Most ophthalmologists intervene soon after patients reach 1 year of age. The rate of nasal endoscopy increases with successive interventions, especially to aid with nasal intubation, either alone or with the assistance of ear, nose, and throat surgeons.


Development and evaluation of a cucumber TILLING population.
Ordered collections of mutants serve as invaluable tools in biological research. TILLING (Targeting Induced Local Lesions IN Genomes) provides an efficient method to discover, in mutagenized populations, the possible phenotypes controlled by gene sequences whose function is unknown. This method can replace transgenic techniques for the functional validation of cloned genes, especially in the case of transformation-recalcitrant plants such as cucumber. We report the development of a TILLING cucumber population, generated by EMS mutagenesis in the Poinsett76 genetic background. The population was evaluated by screening for morphological mutations, and a range of developmental, pigmentation and spontaneous lesion mutants were observed. Suitability for detecting single nucleotide polymorphism in selected genes has been tested by screening a sample of amplicons, with detection rate of 1 SNP in ~1 Mbp. The population described in this Research Note represents a useful asset in cucumber research, to be exploited for forward genetic screens and functional genomics purposes.


Effects of red light cameras on violations and crashes: a review of the international literature.
Red light running is a frequent cause of motor vehicle crashes and injuries. A primary countermeasure for red light running crashes is police traffic enforcement. In recent years, many police agencies have begun using automated red light cameras as a supplement to conventional enforcement methods. The present study reviewed and evaluated available evidence in the international literature regarding the effectiveness of cameras to reduce both red light violations and crashes. Camera enforcement generally reduces violations by an estimated 40-50%. In terms of crash effects, most studies contain methodological flaws that, to varying degrees, either overestimate (failure to adjust for regression to the mean) or underestimate (comparison with nearby signalized intersections affected by cameras) crash effects. Mindful of these limitations, the research generally indicates that camera enforcement can significantly reduce injury crashes at signalized intersections, in particular right-angle injury crashes. Most studies reported increases in rear-end crashes following camera installation. Taken together the studies indicate that, overall, injury crashes, including rear-end collisions, were reduced by 25-30% as a result of camera enforcement.


Real-Time Underwater Image Recognition with FPGA Embedded System for Convolutional Neural Network.
The underwater environment is still unknown for humans, so the high definition camera is an important tool for data acquisition at short distances underwater. Due to insufficient power, the image data collected by underwater submersible devices cannot be analyzed in real time. Based on the characteristics of Field-Programmable Gate Array (FPGA), low power consumption, strong computing capability, and high flexibility, we design an embedded FPGA image recognition system on Convolutional Neural Network (CNN). By using two technologies of FPGA, parallelism and pipeline, the parallelization of multi-depth convolution operations is realized. In the experimental phase, we collect and segment the images from underwater video recorded by the submersible. Next, we join the tags with the images to build the training set. The test results show that the proposed FPGA system achieves the same accuracy as the workstation, and we get a frame rate at 25 FPS with the resolution of 1920 × 1080. This meets our needs for underwater identification tasks.


Formal analysis of the surgical pathway and development of a new software tool to assist surgeons in the decision making in primary breast surgery.
The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities.


High-Level Secretory Expression and Purification of Recombinant Human Interleukin 1 Beta in Pichia pastoris.
As an important pro-inflammatory cytokine, interleukin-1beta (IL-1β) participates in a variety of physiological and pathological responses. In order to obtain higher yielded recombinant human interleukin-1 beta (rhIL-1β), we cloned hIL-1β cDNA sequences based on the coding sequence of human mature IL-1β. After recombinant pPICZαA/hIL-1β was separated and sequenced, we transformed recombinant pPICZαA/hIL-1β into Pichia pastoris GS115, SMD1168 and X-33 strain via electroporation. The results showed that recombinant pPICZαA/ hIL-1β had the highest expression level in X-33 Pichia pastoris. Subsequently, rhIL-1β was purified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and identified by Western blot. Then the fermentation process was optimized to increase product yield. Under the fermentation conditions of the absorption value of fermentation liquor before induction of 600, oxygen concentration of 20%, methanol concentration of 0.25% with pH 5.0, the yield of rhIL-1β reached to 250 mg/L after 72 h induction at 26°C. After aqueous two-phase extraction combined with chromatography, the purity of rhIL-1β was 95% and the yield was up to 85%. The biological activity of rhIL-1β was detected by MTT assay, and the result showed that rhIL-1β significantly inhibited the growth and proliferation of B16 melanoma cells.


[Value of magnetic resonance imaging T2* tests in detecting heart and liver iron overload in patients with β-thalassemia major].
To assess the value of magnetic resonance imaging T2* tests in the detection of myocardial and liver iron overload in patients with β-thalassemia major (β-TM). From 2010 to 2011, 28 β-TM patients over 10 years old under blood transfusion therapy and chelation care with serum ferritin (SF)>1000 µg/L underwent myocardial and liver MRI T2* tests on a voluntary basis. The results were analyzed in relation with age, SF, and left ventricular ejection fraction (LVEF). Fourteen out of the 28 cases (50%) were found to have myocardial iron overload, including 7 severe cases, 2 moderate cases, and 5 mild cases. All the 28 cases had liver iron overload, including 2 mild cases, 7 moderate cases, and 19 severe cases. Two out of the 28 cases had lowered LVEF (7.14%), and one of them had severe myocardial iron overload. There was a negative correlation between myocardial MRI T2* and SF (r=-0.479, P=0.01). Myocardial MRI T2* was positively correlated with liver MRI T2* (r=0.378, P=0.047). Age was not significantly correlated with SF, LVEF, or liver MRI T2*. Magnetic resonance imaging (T2*) detection is an effective and non-invasive means for detecting myocardial and liver iron overload in patients with β-thalassemia major receiving blood transfusion. T2* combined with SF is the main diagnostic indicator to assess iron overload in the vital organs.


Ultra-sensitive analysis of a cantilevered single-walled carbon nanocone-based mass detector.
The ultra-sensitivity of mass detectors using individual cantilevered single-walled carbon nanocone (SWCNC) resonators is first investigated. A higher-order gradient theory, derived at the atomic level, is applied for modeling SWCNC resonators. Numerical simulations using a mesh-free computational framework based on moving Kriging interpolation are conducted to investigate the mass sensitivity of cantilevered SWCNC resonators with extra mass loading as well as with equivalent single-walled carbon nanotube (SWCNT) resonators. Comparison of the magnitude of resonant frequency shifts, the key criterion for mass sensitivity, of these two kinds of resonators demonstrates a far higher mass sensitivity for SWCNC resonators than for SWCNT resonators, thus suggesting a new method for ultra-sensitive mass detection via SWCNC resonators. The dependence of the mass sensitivity of SWCNC resonators on height and top radii has been examined. A reduction in the height of SWCNC resonators gives rise to a considerable increase in mass sensitivity. The mass sensitivity of a 6 nm high SWCNC resonator can even reach a level of 10(-22) g. It is noteworthy that the top radii of SWCNC resonators have a slight effect on frequency shifts. Another interesting observed phenomenon is that a deviation in the height of 19.2° SWCNC resonators leads to little loss in precision of mass detection when the attached mass is smaller than 10(-20) g. This superior characteristic indicates that SWCNC-based mass detectors have great potential in practical applications.


Regulation of mitochondrial function by forkhead transcription factors.
Mitochondria play a central role in several important cellular processes such as energy production, apoptosis, fatty acid catabolism, calcium regulation, and cellular stress response. Multiple nuclear transcription factors have been reported for their role in the regulation of mitochondrial gene expression. More recently, the role of the forkhead family of transcription factors in various mitochondrial pathways has been reported. Among them, FOXO1, FOXO3a, FOXG1, and FOXM1 have been reported to localize to the mitochondria, of which the first two have been observed to bind to the mitochondrial D-loop. This suggests an important role for forkhead transcription factors in the direct regulation of the mitochondrial genome and function. Forkheads such as FOXO3a, FOXO1, and FOXM1 are involved in the cellular response to oxidative stress, hypoxia, and nutrient limitation. Several members of the forkhead family of transcription factors are also involved in the regulation of nuclear-encoded genes associated with the mitochondrial pathway of apoptosis, respiration, mitochondrial dynamics, and homeostasis.


Electron-transfer-catalyzed dimerization of trans-anethole: detection of the distonic tetramethylene radical cation intermediate by extractive electrospray ionization mass spectrometry.
The desolvating droplets of EESI were used as microreactor for the mass spectrometric study of short-lived transients of reactions in condensed liquid phase in the millisecond time region. The electron-transfer-catalyzed dimerization of trans-anethole was investigated and the intermediates in the radical cation chain reaction were isolated and characterized by MS-MS. The distonic tetramethylene radical cation 3(o)(*+) was detected as intermediate, and its cyclization to give the cyclobutane radical cation 3(c)(*+) was observed giving strong evidence that the reaction takes place stepwise.


Nanoscale graft copolymer templates decorated by silver bromide nanoparticles arrays.
A novel amphiphilic poly(4-vinyl pyridine)-graft-poly(lauryl methacrylate) (P4VP-g-PLMA) graft copolymer at 29:71 wt% was synthesized via free radical polymerization, as confirmed by nuclear magnetic resonance (1H NMR). This self-assembled copolymer was used to template the in-situ growth of silver bromide (AgBr) nanoparticles, producing a solid-state nanocomposite film. Interestingly enough, AgBr nanoparticles with a bimodal size distribution were selectively grown within the copolymer matrix. Large nanoparticles with diameters of 30-40 nm were formed in the center of the hydrophilic P4VP spherical domains whereas smaller particles with diameters of 8-10 nm were decorated in hydrophobic PLMA domains. To the best of our knowledge, this is the first report on the nanoscale decoration of amphiphilic copolymer by AgBr nanoparticles with a size-selective, bimodal size distribution.


[Clinical study of urinary cytology in bladder tumors--analysis of factors related with positivity of urinary cytology].
To clarify the clinical and pathological determinants affecting the sensitivity of urinary cytology, we reviewed cytological findings from 119 patients with bladder cancer who were initially treated between January 1982 and March 1988. Cytological specimens obtained from voided urine were stained by the Giemsa and Papanicolaou techniques, and were classified into three categories of malignant cells: positive, suspicious, and negative. Of 311 specimens examined, 114 (37%) were positive, 81 (26%) were suspicious, and the remaining 116 (37%) were negative. The overall positive rate, or sensitivity, was 50% (60 out of 119 patients). The sensitivities were 7% for patients with grade 1 tumors, 42% for grade 2 tumors, and 97% for grade 3 tumors. Univariate analysis by logistic regression analysis revealed that grade, stage, histological pattern of growth, size and number of tumors, and patient age were significantly related with the positivity of voided urinary cytology. The logistic regression model, as a multivariate analysis, demonstrated that grade was the most important determinant affecting the positive cytologic finding, followed by number of tumors with statistical significance. We conclude that the lower sensitivity in conventional urinary cytology for low-grade tumors necessitates new adjuncts, including immunocytochemistry and flow cytometry, to lower the false-negative rate.


Excessive motor overflow reveals abnormal inter-hemispheric connectivity in Friedreich ataxia.
This study sought to characterise force variability and motor overflow in 12 individuals with Friedreich ataxia (FRDA) and 12 age- and gender-matched controls. Participants performed a finger-pressing task by exerting 30 and 70 % of their maximum finger force using the index finger of the right and left hand. Control of force production was measured as force variability, while any involuntary movements occurring on the finger of the other, passive hand, was measured as motor overflow. Significantly greater force variability in individuals with FRDA compared with controls is indicative of cortico-cerebellar disruption affecting motor control. Meanwhile, significantly greater motor overflow in this group provides the first evidence of possible abnormal inter-hemispheric activity that may be attributable to asymmetrical neuronal loss in the dentate nucleus. Overall, this study demonstrated a differential engagement in the underlying default processes of the motor system in FRDA.


Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis.
Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients' individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given.


A multivariate approach to modeling shapes of individual lactation curves in cattle.
Milk test-day records of 5728 lactations of Italian Simmental cows were analyzed with multivariate factor analysis in order to extract 2 common factors, whose scores were used as quantitative measures of 2 main features of lactation curve shape-i.e., the increasing rate of yield in the first part of lactation and the rate of decline of milk yield after the lactation peak. The 2 indices, objectively derived from the correlation matrix of original test-day records, showed a high discriminant power in separating lactation curves with different shapes. The weak correlation between the 2 factors (0.11), together with the high correlation of factors and the total 305-d yield (about 0.70), suggests that an increase in lactation yield could be achieved by acting only on one of the 2 factors related to lactation-curve shape, with the other kept constant at a medium or low value. The suitability of the 2 factors as descriptors of lactation patterns has been confirmed by the relationships found between factor scores and the main environmental effects known to affect the shape of the lactation curve, such as parity and season of calving.


Teaching about health care disparities in the clinical setting.
Clinical teachers often observe interactions that may contribute to health care disparities, yet may hesitate to teach about them. A pedagogical model could help faculty structure teaching about health care disparities in the clinical setting, but to our knowledge, none have been adapted for this purpose. In this paper, we adapt an established model, Time-Effective Strategies for Teaching (TEST), to the teaching of health care disparities. We use several case scenarios to illustrate the core components of the model: diagnose the learner, teach rapidly to the learner's need, and provide feedback. The TEST model is straightforward, easy to use, and enables the incorporation of teaching about health care disparities into routine clinical teaching.


Immunomodulation of Skin Cancer.
Skin cancer represents a major public health issue with a tremendous cost to healthcare systems in the United States and worldwide [...].


Childhood asthma and adult lung function.
An age-matched group of 247 subjects who had had asthma as children and 39 control subjects were studied with lung function and bronchial reactivity testing at the age of 28 years. Lung function of those who had ceased wheezing was essentially normal, but lung function was increasingly abnormal in those who continued to wheeze. Those with frequent wheezing at 28 demonstrated a greater decline in their respiratory function since the age of 7 years than the other groups. Methacholine provocation testing was performed in 91% of the group and was associated with frequency of wheezing and evidence of small airways obstruction. No association was found between reactivity and loss of ventilatory capacity since 21 years of age.


Modulation of the pancreatic islet beta-cell-delayed rectifier potassium channel Kv2.1 by the polyunsaturated fatty acid arachidonate.
Glucose stimulates both insulin secretion and hydrolysis of arachidonic acid (AA) esterified in membrane phospholipids of pancreatic islet beta-cells, and these processes are amplified by muscarinic agonists. Here we demonstrate that nonesterified AA regulates the biophysical activity of the pancreatic islet beta-cell-delayed rectifier channel, Kv2.1. Recordings of Kv2.1 currents from INS-1 insulinoma cells incubated with AA (5 mum) and subjected to graded degrees of depolarization exhibit a significantly shorter time-to-peak current interval than do control cells. AA causes a rapid decay and reduced peak conductance of delayed rectifier currents from INS-1 cells and from primary beta-cells isolated from mouse, rat, and human pancreatic islets. Stimulating mouse islets with AA results in a significant increase in the frequency of glucose-induced [Ca(2+)] oscillations, which is an expected effect of Kv2.1 channel blockade. Stimulation with concentrations of glucose and carbachol that accelerate hydrolysis of endogenous AA from islet phosphoplipids also results in accelerated Kv2.1 inactivation and a shorter time-to-peak current interval. Group VIA phospholipase A(2) (iPLA(2)beta) hydrolyzes beta-cell membrane phospholipids to release nonesterified fatty acids, including AA, and inhibiting iPLA(2)beta prevents the muscarinic agonist-induced accelerated Kv2.1 inactivation. Furthermore, glucose and carbachol do not significantly affect Kv2.1 inactivation in beta-cells from iPLA(2)beta(-/-) mice. Stably transfected INS-1 cells that overexpress iPLA(2)beta hydrolyze phospholipids more rapidly than control INS-1 cells and also exhibit an increase in the inactivation rate of the delayed rectifier currents. These results suggest that Kv2.1 currents could be dynamically modulated in the pancreatic islet beta-cell by phospholipase-catalyzed hydrolysis of membrane phospholipids to yield non-esterified fatty acids, such as AA, that facilitate Ca(2+) entry and insulin secretion.


Effects of Cymbopogon citratus Stapf water extract on rat antioxidant defense system.
Cymbopogon citratus, Stapf(CCS) is commonly known as lemon grass. Previous studies showed that it has a strong antioxidant property and have been traditionally used as analgesic, antipyretic, antiseptic in SoutheastAsia. However, the effect of CCS on antioxidant defense system has not been demonstrated. The present study was conducted to investigate the effects of CCS water extract on rat antioxidant defense system, especially on the expression of y-glutamylcysteine ligase (γ-GCL) and heme oxygenase-1 (HO-1). The CCS water extract was screenedfor its phytochemical contents and antioxidant activity in vitro. Moreover, the extract was studied in rats to evaluate its effects in vivo. Male Sprague-Dawley rats aged eight weeks (250±20 g) were orally administered with CCS at 250, 500 and 1,000 mg/kg/day for one month. The extract contained flavonoids (496.17 mg gallic acid/g CCS extract) and phenolic compounds (4,020.18 mg catechin/g CCS extract). The scavenging activity (DPPH assay) of the extract was demonstrated by EC50 of 917.76±86.89 μg/ ml whereas the EC50 of the potent antioxidant, vitamin C was 31.22±1.84 μg/ml. In the animals, the protein expression of antioxidant enzymes, γGCL and HO-1 was significantly increased in the high dose-treated animals (1,000 mg/kg/day). This was consistent with elevation ofserum total antioxidant capacity. Taken together the present study provides evidence that CCS water extract exhibits antioxidant activity and antioxidant enzymes induction in vivo.


Symptomatic bilateral complete discoid medial menisci of the knee in a child: A case report.
Bilateral complete discoid medial menisci are extremely rare congenital anatomic variants of the knee. Currently, arthroscopic partial meniscectomy with or without peripheral suture repair is performed for symptomatic discoid meniscus. However, most of the outcomes are short-term. In this article, we present a pediatric case of symptomatic bilateral complete discoid medial menisci and highlight the effectiveness of arthroscopic partial meniscectomy with or without peripheral suture on symptomatic complete discoid medial menisci based on 60-month excellent clinical and functional results.


[The incidence of hyperthyroidism in the Suhl district in 1985 and 1987].
An increase of the number of treated hyperthyroidosis-patients within 2 years until 174% was found out in the years 1985 and 1987 by a comparative prescription analysis in the course of 3 months. Sex- and age incidence of the patients did not change in the control period. A more effective iodine prophylaxis of the population has to be supposed as cause for it. The portion of treated patients in the district increased on an average from 7.6 patients/10,000 population in 1985 to 13.2 patients/10,000 population in 1987.


[News of the inquiry about nursing needs and resources in the Brazilian Journal of Nursing (1955-1958)].
Social historical study that has as object news related to the Assessment of the Resources and Needs of Nursing in Brazil published in the Revista Brasileira de Enfermagem between 1955 and 1958. The primary source is constituted of copies of Revista Brasileira de Enfermagem published within the selected period of the study. The secondary sources are constituted of books, papers, dissertations and thesis related to the Nursing history. The data analysis was supported by the secondary sources and the thought of the sociologist Pierre Bourdieu. The results evidenced that Revista Brasileira de Enfermagem, in addition to making possible the dissemination of news about the Assessment provided visibility to it and, at last, had the symbolic effect of giving power and prestige to the Brazilian Nursing.


Development of Nanofiber Sponges-Containing Nerve Guidance Conduit for Peripheral Nerve Regeneration in Vivo.
In the study of hollow nerve guidance conduit (NGC), the dispersion of regenerated axons always confused researchers. To address this problem, filler-containing NGC was prepared, which showed better effect in the application of nerve tissue engineering. In this study, nanofiber sponges with abundant macropores, high porosity, and superior compressive strength were fabricated by electrospinning and freeze-drying. Poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofiber sponges were used as filler to prepare three-dimensional nanofiber sponges-containing (NS-containing) NGC. In order to study the effect of fillers for nerve regeneration, hollow NGC was set as control. In vitro cell viability studies indicated that the NS-containing NGC could enhance the proliferation of Schwann cells (SCs) due to the macroporous structure. The results of hematoxylin-eosin (HE) and immunofluorescence staining confirmed that SCs infiltrated into the nanofiber sponges. Subsequently, the NS-containing NGC was implanted in a rat sciatic nerve defect model to evaluate the effect in vivo. NS-containing NGC group performed better in nerve function recovery than hollow NGC group. In consideration of the walking track and triceps weight analysis, NS-containing NGC was close to the autograft group. In addition, histological and morphological analyses with HE and toluidine blue (TB) staining, and transmission electron microscope (TEM) were conducted. Better nerve regeneration was observed on NS-containing NGC group both quantitatively and qualitatively. Furthermore, the results of three indexes' immuno-histochemistry and two indexes' immunofluorescence all indicated good nerve regeneration of NS-containing NGC as well, compared with hollow NGC. The results demonstrated NS-containing NGC had great potential in the application of peripheral nerve repair.


DEMONSTRATION OF ACID PHOSPHATASE-CONTAINING GRANULES AND CYTOPLASMIC BODIES IN THE EPITHELIUM OF FOETAL RAT DUODENUM DURING CERTAIN STAGES OF DIFFERENTIATION.
Dense cytoplasmic bodies surrounded by one or two unit membranes and containing mitochondria, vesicles, ribosomes, rough and smooth surfaced endoplasmic reticulum, and lamellated membranes (myelin figures) have been observed in the differentiating mucosa of the duodenum of rat foetuses by electron microscopy. Generally, the cytoplasmic components in the bodies seem to be in varying stages of disintegration. The bodies are found in greatest number on the 17th and 18th day of gestation, i.e. at the onset of differentiation. At this period of development the epithelium is stratified, and the villus formation is initiated by invagination of the epithelium by buds of mesenchyme followed by a splitting of the epithelium along the sides of the invaginations. When the villi have formed, the stratified epithelium has changed to the simple columnar type and the dense bodies have largely disappeared. Simultaneously, the lumen has widened considerably. In a parallel study with the light microscope, frozen sections incubated for the demonstration of acid phosphatase activity revealed the reaction product to be localized in bodies of the same size and distribution as the dense bodies found by electron microscopy. Hence, it seems that the bodies are altered and enlarged lysosomes (cytolysomes) active during the intensive differentiative events in the small intestine during the last part of intra-uterine life.


Receptor specificity and trigemino-vascular inhibitory actions of a novel 5-HT1B/1D receptor partial agonist, 311C90 (zolmitriptan).
1. 311C90 (zolmitriptan zomig: (S)-4[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-2-oxazolidinone) is a novel 5-HT1B/1D receptor agonist with proven efficacy in the acute treatment of migraine. Here, we describe the receptor specificity of the drug and its actions on trigeminal-evoked plasma protein extravasation into the dura mater of the anaesthetized guinea-pig. 2. At the "5-HT1B-like' receptor mediating vascular contraction (rabbit saphenous vein), the compound was a potent (p[A50] = 6.79 +/- 0.06) partial agonist achieving 77 +/- 4% of the maximum effect to 5-hydroxytryptamine (5-HT). In the same experiments, sumatriptan (p[A50] = 6.48 +/- 0.04) was half as potent as 311C90 and produced 97 +/- 2% of the 5-HT maximum effect. Studies in which receptor inactivation methods were used to estimate the affinity (pKA) and efficacy relative to 5-HT (tau rel) for each agonist confirmed that 311C90 exhibits higher affinity than sumatriptan (pKA = 6.63 +/- 0.04 and 6.16 +/- 0.03, respectively) and that both drugs are partial agonists relative to 5-HT (tau rel = 0.61 +/- 0.03 and 0.63 +/- 0.10, respectively, compared to 5-HT = 1.0). 3. Consistent with its effects in rabbit saphenous vein, 311C90 also produced concentration-dependent contractions of primate basilar artery and human epicardial coronary artery rings. In basilar artery, agonist potency (p[A50] = 6.92 +/- 0.07) was similar to that demonstrated in rabbit saphenous vein, again being 2-3 fold higher than for sumatriptan (p[A50] = 6.46 +/- 0.03). Both agonists produced about 50% of the maximum response obtained with 5-HT in the same preparations. In rings of human coronary artery, the absolute potency of 311C90 and sumatriptan was higher than in primate basilar artery (p[A50] = 7.3 +/- 0.1 and 6.7 +/- 0.1, respectively), but maximum effects relative to 5-HT were lower (37 +/- 8% and 35 +/- 7%, respectively). In both types of vessel, the inability of 5-HT1B/1D agonists to achieve the same maximum as the endogenous agonist 5-HT is explained by the additional presence of 5-HT2A receptors. 4. 311C90 displayed high affinity at human recombinant 5-HT1D (formerly 5-HT1D alpha) and 5-HT1B (formerly 5-HT1D beta) receptors in transfected CHO-K1 cell membranes (pIC50 values = 9.16 +/- 0.12 and 8.32 +/- 0.09, respectively). In intact cells, the drug produced concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase (p[A50] = 9.9 and 9.5, respectively) achieving the same maximum effect as 5-HT. Excepting human recombinant 5-HT1A and 5-ht1F receptors at which the drug behaved as an agonist with modest affinity (pIC50 = 6.45 +/- 0.11 and 7.22 +/- 0.12, respectively), 311C90 exhibited low, or no detectable affinity (pKi or pKB < or = 5.5) at numerous other monoamine receptors, including other 5-HT receptor subtypes. 5. When administered to anaesthetized guinea-pigs ten minutes before unilateral electrical stimulation of the trigeminal ganglion (1.2 mA, 5 Hz, 5 ms, 5 min), 311C90 (3-30 micrograms kg-1, i.v.) caused a dose-dependent inhibition of [125I]-albumin extravasation within the ipsilateral dura mater. At the same doses, the drug also produced dose-dependent falls in cranial vascular conductance (32.3 +/- 7.5% at 30 micrograms kg-1), as measured in the ear by laser doppler flowmetry. 6. These results show that 311C90, a novel member of the 5-HT1B/1D agonist drug class, exhibits a high degree of pharmacological specificity. Its potent partial agonist action at "5-HT1B-like' receptors in intracranial arteries, coupled with potent agonism at 5-HT1D and 5-HT1B receptors and an ability to inhibit neurogenic plasma protein extravasation in the dura, are consistent with its utility as an effective acute treatment for migraine.


Renal neuroendocrine control of desiccation and cold tolerance by Drosophila suzukii.
Neuropeptides are central to the regulation of physiological and behavioural processes in insects, directly impacting cold and desiccation survival. However, little is known about the control mechanisms governing these responses in Drosophila suzukii. The close phylogenetic relationship of D. suzukii with Drosophila melanogaster allows, through genomic and functional studies, an insight into the mechanisms directing stress tolerance in D. suzukii. Capability (Capa), leucokinin (LK), diuretic hormone 44 (DH44 ) and DH31 neuropeptides demonstrated a high level of conservation between D. suzukii and D. melanogaster with respect to peptide sequences, neuronal expression, receptor localisation, and diuretic function in the Malpighian tubules. Despite D. suzukii's ability to populate cold environments, it proved sensitive to both cold and desiccation. Furthermore, in D. suzukii, Capa acts as a desiccation- and cold stress-responsive gene, while DH44 gene expression is increased only after desiccation exposure, and the LK gene after nonlethal cold stress recovery. This study provides a comparative investigation into stress tolerance mediation by neuroendocrine signalling in two Drosophila species, providing evidence that similar signalling pathways control fluid secretion in the Malpighian tubules. Identifying processes governing specific environmental stresses affecting D. suzukii could lead to the development of targeted integrated management strategies to control insect pest populations. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Study of a new low molecular weight heparin (LU 47311) administered to healthy volunteers.
A newly developed low molecular weight heparin (LU 47311) was given to 6 healthy volunteers (males, mean age: 30.5 years, range: 20-39 years). They obtained a single dose of 40 and 60 anti FXaU per kg body weight, respectively, by subcutaneous administration. The anti FXa elimination half-life was close to 3 hours. The APTT showed slight response following high dose. No significant influence on fibrinolysis as measured by t-PA and PAI assays was noticed. There was no clear evidence of enhancement of platelet function when detected by Born's method and platelet factor 4 and beta-thromboglobulin assays. However, a moderate but significant increase of thromboxane B2 was noticed in the group obtaining an elevated dose of LMW heparin. Serum levels of triglycerides and cholesterol remained unaltered. The aminotransferases, electrolytes, renal function parameters and cell counts of the peripheral blood were not influenced by LMW heparin.


Analysis of the Individual Set-Pieces Influence on the Teams' Ranking in Rink Hockey.
The main objective of this research was to analyze the individual set-pieces influence on the final season ranking in rink hockey. For this purpose, 6,920 individual set-pieces from 1,680 matches corresponding to free direct hits (n = 4,332) and penalty shots (n = 2,588) were analyzed during seven consecutive seasons (2012-13 to 2018-19) in the First Spanish League (Ok Liga). The variables recorded were the following for each team: total points, free direct hits attempted, free direct hits scored, penalties attempted, penalties scored, total goals scored during the season, free direct hits received, goals received from free direct hits, penalties received, goals received from penalties and total goals received in the season. Results showed that 21.08% of the goals were scored by free direct hits and penalty shots (11.58% and 9.49%, respectively). Likewise, teams ranked in a better position achieved higher effectiveness in individual set-pieces and their goalkeepers were more effective in defending the free direct hits and penalties. Furthermore, results showed significant correlations between team season points and better performance in individual set-pieces variables. Therefore, the results of this study demonstrated the importance of systematic practice of free direct hits and penalty shots for teams' success in rink hockey. Additionally, it is suggested that teams possess special players to execute these particular elements of match play.


Cross-cultural adjustment of Chinese students in Japan.
The present study examined responses of 92 Chinese students in Japan to questionnaires which included adjustment items selected from work of Baker in 1981 and Uehara in 1988. These items were classified by factor analysis into four scales of Emotional, Academic, Cultural-Social, and Environmental. Adjustment scores on the Environmental scale were higher than those on the other three scales. Country of origin was a significant influence only for scores on the Environmental scale. Students who came from Taiwan scored higher on adjustment. There were gender differences on Emotional and Academic scales; male students reported higher adjustment. The effects of students' length of residence and proficiency in the Japanese language could be seen in scores on Academic and Cultural-Social scales; the students who had a longer period of stay or had higher proficiency in Japanese language had higher scores on adjustment. Thus, results indicated that personal differences were reflected in subfactors of adjustment.


Transcriptome and Metabolome Integration Provides New Insights Into the Regulatory Networks of Tibetan Pig Alveolar Type II Epithelial Cells in Response to Hypoxia.
Tibetan pigs show a widespread distribution in plateau environments and exhibit striking physiological and phenotypic differences from others pigs for adaptation to hypoxic conditions. However, the regulation of mRNAs and metabolites as well as their functions in the alveolar type II epithelial (ATII) cells of Tibetan pigs remain undefined. Herein, we carried out integrated metabolomic and transcriptomic profiling of ATII cells between Tibetan pigs and Landrace pigs across environments with different oxygen levels to delineate their signature pathways. We observed that the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) profiles displayed marked synergy of hypoxia-related signature pathways in either Tibetan pigs or Landrace pigs. A total of 1,470 DEGs shared between normoxic (TN, ATII cells of Tibetan pigs were cultured under 21% O2; LN, ATII cells of Landrace pigs were cultured under 21% O2) and hypoxic (TL, ATII cells of Tibetan pigs were cultured under 2% O2; LL, ATII cells of Landrace pigs were cultured under 2% O2) groups and 240 DAMs were identified. Functional enrichment assessment indicated that the hypoxia-related genes and metabolites were primarily involved in glycolysis and aldosterone synthesis and secretion. We subsequently constructed an interaction network of mRNAs and metabolites related to hypoxia, such as guanosine-3', 5'-cyclic monophosphate, Gly-Tyr, and phenylacetylglycine. These results indicated that mitogen-activated protein kinase (MAPK) signaling, aldosterone synthesis and secretion, and differences in the regulation of MCM and adenosine may play vital roles in the better adaptation of Tibetan pigs to hypoxic environments relative to Landrace pigs. This work provides a new perspective and enhances our understanding of mRNAs and metabolites that are activated in response to hypoxia in the ATII cells of Tibetan pigs.


End-of-life cost trajectories and the trade-off between treatment costs and life-extension: Findings from the Cost and Medical Care of Patients with Advanced Serious Illness (COMPASS) cohort study.
Few studies have assessed how patient preferences influence end-of-life costs. To estimate mean monthly healthcare costs in 2019 Singapore Dollars (SGD) at five time points within the last year of life and identify how patients' preferences for the trade-off between treatment cost containment and life-extension and other factors affect these costs. Mean monthly costs were quantified in the last 1, 3, 6, 9, and 12-months before death. Univariate and multivariate analyses were conducted. Billing records for 286 deceased participants in the Cost and Medical Care of Patients with Advanced Serious Illness (COMPASS) cancer cohort study in Singapore. Mean monthly costs were $5140 (95% CI: $4750; $5520) in the 12-months before death and rose to $8350 (95% CI: $7110; $9590) 1-month before death. Participants preferring higher cost containment/less life-extension defied the trend of increasing costs closer to death (mean monthly costs of $4630 (95% CI: $3690; $ 5580) and $4850 (95% CI: $2850; $6850) (12-months and 1-month before death respectively). Participants preferring lower cost containment/more life-extension had costs that were $1050 (95% CI: $49; $2051) and $5220 (95% CI: $2320; $8130) higher than those preferring lower costs/less life-extension 12-months and 1-month before death respectively. On average, cancer patients in Singapore can expect to spend $61,680 in the last year of life. Of broader relevance is that patient preferences and other observable factors clearly influence these costs, suggesting that policymakers and patients can better predict and budget for end-of-life costs by considering these factors.


A field study on the effect of in-feed inclusion of a natural zeolite (clinoptilolite) on health status and performance of sows/gilts and their litters.
The study was conducted to evaluate the effect of the long-term dietary use of a natural zeolite (clinoptilolite, NZ) on health status and reproductive performance of sows/gilts and performance of their litters, along with its compatibility with antibacterials (chlortetracycline, CTC) periodically used in medication programmes. Two hundred and forty sows/gilts and their litters were assigned to two main experimental groups and four subgroups, depending on the inclusion of NZ and CTC in their feed. During the trial, frequent sampling of pregnancy feed for mycotoxicological analysis revealed a high contamination level with zearalenone. No adverse or side effects attributed to NZ were noticed. Furthermore, the combined use of NZ and CTC revealed no clinically apparent interactive effect on the availability of the latter. Reproductive performance was significantly improved by the dietary inclusion of both NZ and CTC. The results also suggested that the beneficial effect of NZ could be additionally considered as an indicator of the amelioration of zearalenone exposure consequences.


Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate.
The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), which has an annual mortality rate of ~800,000. Although surgical procedures for HCC, such as hepatic resection and liver transplantation, have progressed and the outcomes of patients have improved, HCC is still characterized by frequent recurrence, even after liver transplantation. In the present study the expression of the protein coding gene, S100 calcium binding protein A3 (S100A3), was observed in 62 HCC tissues and tumor-surrounding tissues. The present study indicated that S100A3 activation was involved in tumorigenesis and tumor aggressiveness. The protein and mRNA expression levels of S100A3 in the human HCC cell line (HepG2) were investigated using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, respectively. The function of sodium cantharidinate in inducing HCC cell apoptosis was also investigated. Sodium cantharidinate inhibited the protein and gene expression of S100A3 in HepG2 cells in vitro. These data suggested that S100A3 has an important role in human HCC. The present study indicates that the functional properties of sodium cantharidinate are promising for the development of a novel drug that may control the expression of S100A3 and improve the treatment of human HCC in the near future.